Global burden of type 2 diabetes in adolescents from 1990 to 2019

Purpose To evaluate the burden of type 2 diabetes (T2D) among adolescents (15–24 years old) from 1990 to 2019. Methods The age-standardized incidence rate (ASIR) and disability-adjusted life years (DALYs) rate of adolescents were analyzed according to age, sex, geographical location, and sociodemographic index (SDI). The estimated annual percentage change (EAPC) was estimated to quantify the trends. Results From 1990 to 2019, the ASIR (EAPC = 1.07) and age-standardized DALY rate (EAPC = 2.01) of T2D in adolescents showed an increasing trend. The ASIR was higher in males than in females. The burden was greater in the 20–24-year age group. Of the five SDI regions, the highest ASIR and age-standardized DALY rate were found in low-middle-SDI regions, while the greatest increase in these rates was observed in high-SDI regions (EAPC = 3.28 and 3.55, respectively). Of the 21 regions analyzed, the highest ASIR and age-standardized DALY rate were found in Oceania. Of the 204 countries analyzed, the Marshall Islands (651.16) and Kiribati (277.42) had the highest ASIR and DALYs, respectively. The regions with the greatest increase in the ASIR from 1990 to 2019 were Western Europe (EAPC = 4.15), high-income North America (EAPC = 4.72). Conclusions The global burden of T2D in adolescents showed an overall upward trend from 1990 to 2019. It is necessary to strengthen prevention measures related to risk factors for T2D among young people, especially in areas with a low-to-medium SDI.


Introduction
Diabetes is a chronic noninfectious metabolic disease characterized by a high blood glucose concentration.Type 2 diabetes (T2D) is the most common type of diabetes.It accounts for more than 90% of all diagnosed cases of diabetes globally (1) and poses a serious threat to global health (2).In 2019, the number of disability-adjusted life years (DALYs) attributed to diabetes globally was 66.3 million, which makes diabetes the fourth largest cause of disability (3).The global number of diabetes patients is showing a sustained, rapidly increasing trend.In 2019, the global number of diabetes patients was estimated to be 463 million, accounting for 9.3% of the global adult population.By 2030 and 2045, this number is expected to increase to 590 million (10.2%) and 700 million (10.9%) (4,5), respectively, which will place considerable economic pressure on individuals, families, healthcare systems, and society.
Traditionally, T2D has been considered to be a metabolic disorder in middle-aged and older adults but relatively rare in adolescents and young people.However, due to obesity, a highenergy diet, and a sedentary lifestyle, the incidence rate of T2D in adolescents is increasing sharply.Early-onset T2D (diagnosed before the age of 40, i.e., in adolescents aged 15-24 years) is becoming increasingly common and thus deserves special attention.A study in the United States found that children and adolescents are the age groups with the highest T2D incidence rates (6).From 2002-2003 to 2011-2012, the T2D incidence rate in adolescents aged 10-19 years in the United States increased by 4.8% annually (7).Young people with early-onset T2D are exposed to hyperglycemia for longer periods of time than those with late-onset T2D, which increases their risk of microvascular and macrovascular diseases, kidney disease, and other complications (8).The complex manifestations of T2D in patients aged 15-24 years may require decades of intensive treatment (9).Therefore, understanding the global burden of T2D in adolescents (15-24 years old) may facilitate the balancing of medical resources in different regions and provide the basis and guidance for the prevention and treatment of diabetes.
The data used in this study were derived from the Global Burden of Disease (GBD) Study.The data describe the epidemiological characteristics (incidence rate and DALYs) and global burden of T2D in those aged 15-24 years from 1990 to 2019.We compared the global burden for different ages, sexes, regions, sociodemographic index (SDI) values, and countries.Moreover, we evaluated the trend in the burden of T2D from 1990 to 2019 at the global, regional, and national levels, with the aim of formulating relevant strategies to address these trends.

Data source
The data were sourced from the GBD 2019 database published on the website of the Institute for Health Indicators and Evaluation at the University of Washington.The aim of the GBD Study was to assess the global disease burden and health-related data for 369 diseases and injuries and 87 risk factors in 204 countries and regions.We only collected T2D data from those aged 15-24 years, using the Global Health Data Exchange query tool (http:// ghdx.healthdata.org/gbd-results-tool).We obtained the incidence rate and DALY data for T2D in adolescents (15-24 years old) according to age, sex, and region.In addition, considering that there is only a small number of T2D patients aged less than 15 years, we selected those over the age of 15 years and divided them into two age groups (15-19 and 20-24 years) for analysis.This study is based on a publicly available database and does not require ethical approval.

T2D definition
According to the 10th edition of the International Classification of Diseases, the T2D codes are E11-E11.1 and the diagnosis codes are E11.3-E11.9.In the 2019 GDB Study, T2D was defined as a fasting plasma glucose concentration ≥ 126 mg/dL (70 mmoL/L), a 2-h blood glucose concentration ≥ 200 mg/dL (11.1 mmoL/L), and/ or a record of diabetes treatment.

Statistical analysis
An age-standardized rate per 100,000 population is calculated as follows: where a i is the age-specific rate for the ith age group, w i is the number of people in the corresponding ith age subgroup in the selected reference standard population, and A is the number of age groups.
Age standardization aims to eliminate the impact of population age composition and ensure comparability of research indicators.The age-standardized rate in the GBD database is estimated using the world-population age standard (10).Direct standardization results in standardized or age-adjusted rates, which are weighted averages of specific age rates for each population being compared.The weight (standard) is used to represent the relative age distribution of an external population and serves as a summary rate for each population.This rate reflects the number of events that can be expected to occur if the populations being compared have the same age distribution.
EAPC is a widely accepted quantitative indicator used for estimating the annual average change in age-standardized rate within a given period.Fitting was performed based on the natural logarithm of time variables and their corresponding observations, thereby ensuring that each observation contributed to the calculation of EAPCs.Moreover, as EAPC estimates and quantifies the long-term trend in disease burden indicators such as the incidence rate and mortality of diseases.
We established a regression model to describe the relationship between the natural logarithm (ln) of age-standardized rate and time, as defined by y=b0+bx+c, y=In(ASIR), where x=the calendar year, b0 is constant term, c is the false term, and b is the meaning of the negative or positive tendency of the selected age-standardized rate.The EAPC was counted using the following formula: EAPC = 100 × (exp [b] − 1).The 95% confidence interval (CI) of the EAPC was obtained from the linear regression model (11).
If the EAPC and its 95% CI were less than 0, it indicated a downward trend, whereas if the EAPC and its 95% CI were greater than 0, it indicated an upward trend.R software (version 4.1.1)was used for the statistical analyses.

Trends according to sex and age
The male-to-female ASIR ratios for T2D in adolescents (15-24 years old) were 1.07 and 1.11 per 100,000 people globally in 1990 and 2019, respectively, indicating that the ASIR was higher in males than in females.This was true for all of the five SDI regions.In 1990 and 2019, the age-standardized DALY rates for adolescents (15-24 years old) were 0.77 and 0.87 for every 100,000 people, respectively.The age-standardized DALY rate was lower in males than in females, and this was true for all of the five SDI regions (Table 1; Figure 2).
Of the 30 countries with the highest incidence rate and DALY rate in 2019, all except Greenland showed lower incidence rates in the 15-19-year age group than in the 20-24-year age group (Figures 3A, B).Only 17 (Benin, Burkina Faso, Cameroon, Chad, Cote dIvoire, Gambia, Ghana, Guinea, Guinea Bissau, Mali, Mauritania, Niger, Nigeria, Senegal, Sierra Leone, Togo, and Zimbabwe) of the 204 countries analyzed had a higher agestandardized DALY rate in the 15-19-year age group, while only two countries (Greenland and United States) had a higher ASIR in the 15-19-year age group (Supplementary Tables 1, 2; Supplementary Figure 1).1; Figure 1).

T2D burden and its trend by SDI
From 1990 to 2019, the ASIR and age-standardized DALY rate increased to a certain degree in all regions.The ASIR (EAPC = 3.28) and age-standardized DALY rate (EAPC = 3.55) both increased the most in high-SDI regions, while the ASIR and age-standardized DALY rate increased the least in low-SDI regions, with growth rates of ASIR(121%)and ge-standardized DALY rate(17%), respectively (Table 1; Figure 1).
As shown in Figure 4A, in 21 regions, the ASIR for T2D in adolescents (15-24 years old) roughly showed a wave-like trend as the SDI value increased, first increasing, then decreasing, and then increasing again.The ASIR reached its highest level at an SDI value of approximately 0.7, and in Oceania, Central Latin America, South Asia, the Caribbean, and East Asia, it far exceeded the expected level.The relationship between the ASIR, EAPC, and SDI was relatively stable, with the EPAC reaching its lowest level at an SDI value of approximately 0.7.In Western Europe, East Asia, and Southern Latin America, the ASIR growth rate was significant and was much higher than expected.The DALYs associated with adolescents (15-24 years old) showed a wave-like trend according to the SDI value, first increasing and then decreasing as the SDI value increased (Figure 4B).The ASIR increased until an SDI value of 0.7 and then decreased.The relationship between DALYs, the EAPC, and the SDI value also showed a wave-like pattern, with two peaks at SDI values of approximately 0.6 and 0.83, with the largest increase at an SDI value of 0.6.The DALY rates in high-income North America, Western Europe, and East Asia were much higher than the global expectations.
In all 204 countries analyzed, the ASIR and EAPC for adolescents (15-24 years old) first decreased and then increases as the SDI value increased (Supplementary Figure 2A).The ASIR reached its lowest level at an SDI value of approximately 0.75, corresponding to countries such as the Netherlands, Denmark, and Germany.The ASIR showed a continuous downward trend as the SDI value increased to 0.75.Then, as the SDI value increased further above 0.75, most countries showed an increasing trend in the ASIR, with these trends in countries such as Qatar, Guatemala, and Cameroon far exceeding expectations.The relationship between DALYs, the EAPC, and the SDI value showed a similar trend (Supplementary Figure 2B).

Discussion
Our analysis of data from the 2019 GBD Study showed that, from 1990 to 2019, the burden of T2D in adolescents (15-24 years old) showed an upward trend, with the greatest burden in mediumlow-SDI regions and the fastest growth in high-SDI regions.Males were more likely to suffer from T2D, while females showed a higher number of DALYs associated with T2D.The etiology of T2D is complex, and in addition to being influenced by known immutable factors, such as age and genetic factors, there are some factors that can be modified through lifestyle changes.In recent years, the surge in T2D cases has been largely due to lifestyle changes and rapid economic development, continuous urbanization, sedentary lifestyles, and unhealthy dietary patterns are considered to be the main factors driving this growth (12).
Obesity and overweight are recognized as the main risk factors for T2D.In 2016, it was estimated that more than 80% of adolescents and approximately 27.5% of adults globally did not meet the recommended physical activity levels (13).High-energy foods and high-sugar beverages, as well as reduced levels of physical activity, are the main causes of obesity in adolescents and young adults (14).A high body mass index is closely related to insulin resistance, dyslipidemia, and other cardiac metabolic risk factors.The associations between physical activity and sedentary time and the risk of T2D are largely mediated by obesity.Research has shown that the prevalence of obesity among adolescents and young adults has increased globally.Therefore, controlling weight in adolescents is key to reducing the incidence of adolescents (15-24 years old).the discussion on risk factors primarily focuses on factors like diet and physical activity, while other potential contributors to the burden of T2D, such as genetic predisposition and environmental factors, are given less emphasis.
The global burden of T2D among adolescents (aged 15-24 years) showed an overall upward trend from 1990 to 2019; however, there were significant differences according to sex, age, and region.Low-tomedium-SDI regions, such as Oceania, the Marshall Islands, and Kiribati, showed the highest burden.Areas with a high SDI value, such as high-income North America, Western Europe, and the United Kingdom, showed the most rapid increase in the burden of T2D.Thus, it is necessary to strengthen prevention, control, and intervention measures related to risk factors for T2D in adolescents, especially in areas with a low-to-medium SDI value.

FIGURE 1
FIGURE 1The age-standardized DALY rate and the age-standardized incidence rate (ASIR) of type 2 diabetes among adolescents by 21 regions in 2019.(A) Age-standardized DALY Rate by Region (B) ASIR by Region.
FIGURE 4 (A) The relationship between ASIR and EAPC and SDI in 21 regions.(B) The relationship between DALY and EAPC and SDI in 21 regions.

TABLE 1
The age-standardized DALY rate and the age-standardized incidence rate (ASIR) of type 2 diabetes among adolescents in 1990 and 2019, and its temporal trends from 1990 to 2019.